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OBJECTIVE: To observe whether adenosine Al receptor (Al R) mediated neuroprotection of Shenmai Injection (SI) on rat cerebral ischemia/reperfusion (I/R) injury. METHODS: The focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO). Totally 60 successfully modeled rats was divided into 5 groups according to randomized block principle, i.e., the model group, the SI group, the SI + AlR antagonist (1,3-dipropyl-8-cyclopentylxanthine, DPCPX) group, the AlR antagonist control group, and the dimethyl sulfoxide (DMSO) control group, 12 in each group. Besides, a sham-operation group was set up (n =12). SI at 15 mL/kg was peritoneally injected to mice in the SI group immediately after cerebral I/R. Equal volume of normal saline was injected to mice in the model group and the sham-operation group. DPCPX at 1 mg/mL was peritoneally injected to mice in the Al R antagonist control group 30 min before peritoneal injecting SI. DPCPX at 1 mg/kg and DMSO at 1 mL/kg were peritoneally injected to mice in the AlR antagonist control group and the DMSO control group 30 min immediately before cerebral I/R. Rats' neurobehavioral scores were assessed after 24 h reperfusion. The volume of cerebral infarction and Bcl-2 protein expression of cerebral infarction penumbra were also detected. Results Compared with the sham-operation group, neurobehavioral scores, the volume of cerebral infarction, and Bcl-2 protein expression increased (all P <0. 05). Compared with the model group, neurobehavioral scores and the volume of cerebral infarction obviously decreased, but Bcl-2 protein expression increased in the SI group (all P <0. 05). Compared with the SI group, neurobehavioral scores increased, the volume of cerebral infarction was obviously enlarged, and Bcl-2 protein expression was obviously reduced in the A1R antagonist control group (all P <0. 05). CONCLUSIONS: SI's neurobehavioral scores could be partially reversed in the Al R antagonist control group, the volume of cerebral infarction and Bcl-2 protein expression improved. AlR might possibly meditate neuroprotection of SI on MACO mire
Assuntos
Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Neuroproteção/fisiologia , Fármacos Neuroprotetores/farmacologia , Receptor A1 de Adenosina/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Adenosina , Animais , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/uso terapêutico , Infarto da Artéria Cerebral Média , Camundongos , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Sprague-Dawley , XantinasRESUMO
OBJECTIVE: To explore the efficacy difference between electroacupuncture (EA) at "Zusanli" (ST36) and "Baihui" (GV20) for inflammatory pain and cerebral ischemia-reperfusion injury (CIRI) in rats. METHODS: In 1st part of this study, 90 male SD rats were randomly divided into sham-operation, model (induced by occlusion of the middle cerebral artery and reperfusion), GV20 EA, ST36 EAï¼and sham EA groups (n=16 in each group). In the 2nd part of the study, 40 male SD rats were randomized into saline injection (control), inflammatory pain model (subcutaneous injection of complete Freund's adjuvant ï¼»CFAï¼½ into the right paw), ST36 EA, GV20 EA, and sham EA groups (n=8 in each group). In these two parts, EA (2 Hz/15 Hz, 1 mA) was applied to ST36 or GV20. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency ï¼TWLï¼ were detected 2.5 h after administration of CFA by using Von Frey and plantar tester, respectively. The neurological deficit scores (NDS) were assessed by using Longa's method and the infarct size of the brain assessed after staining with 2% triphenyltetrazolium chloride (TTC). The expression of c-fos protein in the dorsal horns (DHs) of the spinal cord was detected by immunohistochemistry. RESULTS: (1) Twenty-four hours following CIRI, the NDS and infarct volume were significantly increased in the model group compared with the sham-operation group (P<0.01), and obviously decreased in the GV20 EA and ST36 EA groups relevant to the CIRI model group (P<0.05, P<0.01). There were no significant differences between the two EA groups in the NDS and infarct volume levels (P>0.05). (2) After administration of CFA, both the MPT and TPT were notably decreased in the inflammatory pain model group in contrast to the saline-injection group (P<0.01), but were considerably increased in both ST36 EA and GV20 EA groups (P<0.05), rather than in the sham EA group (P>0.05). The number of c-fos positive cells was significantly increased in the medial half of I-II and III-IV lamina of DHs in the L4-L6 segments of spinal cord in the inflammatory pain model group relevant to the saline-injection group (P<0.01,P<0.05), and was remarkably decreased in the lamina I-II (not in the deeper lamina) in both ST36 EA and GV20 EA groups (P<0.01), rather than in the sham EA group (P>0.05). No significant differences were found in the number of c-fos positive cells between the ST36 EA and GV20 EA groups (P>0.05). CONCLUSION: Our data do not support the specificity of functions at least between GV20 EA and ST36 EA in both CIRI and inflammatory pain model rats. This is the first study reporting the effect of EA at GV20 for relieving CFA-induced inflammatory pain.
Assuntos
Isquemia Encefálica , Eletroacupuntura , Traumatismo por Reperfusão , Animais , Isquemia Encefálica/terapia , Masculino , Dor/etiologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/terapiaRESUMO
The aim of the study was to examine the correlation between KCNJ11 gene polymorphism and metabolic syndrome in elderly patients. From January 2014 to January 2015, 54 elderly patients with metabolic syndrome were enrolled in this study as the observation group. During the same period, 46 healthy elderly individuals were enrolled in this study as the control group. KCNJ11 gene polymorphism (rs28502) was analyzed using polymerase chain reaction-restriction fragment length polymorphism. The expression levels of mRNA in different genotypes were detected using FQ-PCR. ELISA was used to evaluate the KCNJ11 protein expression in different genotypes. KCNJ11 gene polymorphism and metabolic syndrome was studied by measuring the blood pressure levels in patients with different genotypes. Three genotypes of KCNJ11 gene in rs28502 were CC, CT and TT. The CC, CT and TT genotype frequencies in healthy population were 8.5, 9.2 and 82.2%, respectively, while the genotype frequencies in patients with metabolic syndrome were 42.4, 49.8 and 7.8%, respectively. There were significant differences between groups (P≤0.05). However, the genotype frequencies of C/T in healthy individuals and metabolic syndrome patients were 35.3 and 38.3%, respectively. There were no significant differences between groups (P>0.05). FQ-PCR results showed that the KCNJ11 mRNA expression levels in the control and observation groups had no significant differences (P>0.05). However, the results obtained from ELISA analysis revealed that KCNJ11 protein expression level in the observation group was significantly higher than that in the control group (P<0.05). In conclusion, KCNJ11 gene polymorphism is associated with metabolic syndrome in the elderly. Elderly patients with the CC and TT genotypes are more likely to develop metabolic syndrome.
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BACKGROUND: It has been reported that carnosic acid (CA) exhibits a range of biological activities including hepatoprotective, antioxidant and anti-inflammatory. However, the effect of carnosic acid in neuropathic pain remained elusive. METHODS: A neuropathic pain model of chronic constriction injury (CCI) was established in adult male Sprague-Dawley rats. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were recorded, and western blot was performed to detect sirtuin1 and p66shc content. RESULTS: Intrathecal administration of carnosic acid attenuated mechanical allodynia and thermal hyperalgesia in rats following chronic constriction injury. Interestingly, carnosic acid analgesic effect was positively associated with spinal sirtuin1 activation; however, p66shc was inhibited by carnosic acid in the spinal cord. In additional, sirtuin1 inhibitor EX-527 reversed the anti-nociceptive effect of carnosic acid. CONCLUSIONS: Carnosic acid is effective in the treatment of the established CCI-induced pain. It may be possible that spinal sirtuin1 activition by carnosic acid attenuates neuropathic pain through a mechanism involving the down-regulation of p66shc expression.